Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily activated by fatty acids. The PPAR family consists of PPAR-α, PPAR-β/δ and PPAR-γ, which show different ligand specificity and tissue distribution. PPAR-α is expressed the most in the liver and promotes fatty acid oxidation in peroxisomes and mitochondria. PPAR-γ is expressed in adipose tissues and regulates storage of fats. The ligand of PPAR-α, fibrate, is used as hypolipidemic agent, and the ligand of PPAR-γ, thiazolidinedione, is used in the treatment of diabetes mellitus type 2.
PPAR-δ is expressed in muscles, brown adipose tissues, etc. This transcription factor shows anti-obesity effect since fatty acid oxidation in adipocytes is promoted in mice in which it is overexpressed (Wang Y X et al., Cell, 113, pp. 159-170, 2003). An activator of PPAR-δ promotes metabolism in skeleton muscle cells, improves insulin sensitivity, reduces adipocytes and inhibits inflammatory response by increasing expression of such proteins as carnitine palmitoyltransferase lβ (CPT1β) and pyruvate dehydrogenase kinase isozyme 4 (PDK4) (Barish G D et al., J. Clin. Invest., 116, pp. 590-597, 2006, 116:590). When the ligand of PPAR-δ, GW501516, was administered together with the AMP-activated protein kinase (AMPK) activator AICAR to a mouse, the mouse showed strengthened muscles even without exercise as well as anti-obesity effect (Vihang A N et al., Cell, 134, pp. 1-11, 2008).
However, activator or ligand of PPAR-δ with proven stability has not been found yet. The inventors of the present disclosure have found out that Artemisia iwayomogi extract contains a novel ligand capable of activating PPAR-δ.